Elucidation of alternative developmental pathway of NKT cells from CD4/CD8 double-negative thymocytes

• Project/Area Number: 24790490
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: DASHTSOODOL Nyambayar 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (50443057)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: NKT / 胸腺 / 分化経路 / CD1d / thymus / development / precursor / ナチュラルキラーT（NKT）細胞 / 分化 / 前駆細胞

Outline of Final Research Achievements

Currently it is thought that NKT cells are generated from CD4/CD8 double-positive (DP) thymocytes by selection on CD1d, a process termed the DP pathway. However, it is still unknown whether NKT cells develop exclusively by the DP pathway in a manner closely resembling that of conventional T cells, or some alternatives to this pathway exist. Here we provide genetic evidences demonstrating the presence of an alternative developmental pathway of NKT cells from CD4/CD8 double-negative (DN) stage thymocytes that is before the DP stage by using the DP-specific Rag2 deletion and genetic fate-mapping mouse models. Furthermore, we found that NKT cells generated by the DN pathway possess characteristics of Th1-biased cytotoxic effector cells suggesting this developmental pathway gives rise preferentially to Th1-type NKT cells. Our present findings provide new insights in understanding the development of NKT cells in the thymus, which seems to be different from that of conventional T cells.

Research Products

• [Journal Article] Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire. (2016)
  • Author(s): Dashtsoodol N, Shigeura T, Ozawa R, Harada M, Kojo S, Watanabe T, Koseki H, Nakayama M, Ohara O, Taniguchi M.
  • Journal Title: PLoS ONE Volume: 11 Issue: 4 Pages: 1-10
  • DOI: 10.1371/journal.pone.0153347
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Discovery of NKT cells and development of NKT cell-targeted anti-tumor immunotherapy (2015)
  • Author(s): Taniguchi M, Harada M, Dashtsoodol N, Kojo S.
  • Journal Title: Proceedings of the Japan Academy, Series B Volume: 91 Issue: 7 Pages: 292-304
  • DOI: 10.2183/pjab.91.292
  • NAID: 130005088948
  • ISSN: 0386-2208, 1349-2896
  • Peer Reviewed / Open Access
• [Journal Article] Generation of induced pluripotent stem cell-derived mice by reprogramming of a mature NKT cell. (2014)
  • Author(s): Ren Y, Dashtsoodol N, Watarai H, Koseki H, Quan C, Taniguchi M.
  • Journal Title: International Immunology Volume: 26 Issue: 10 Pages: 551-561
  • DOI: 10.1093/intimm/dxu057
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Generation of induced pluripotent stem cell-derived mice by reprogramming of a mature natural killer T cell. (2014)
  • Author(s): Ren Y, Dashtsoodol N, Watarai H, Koseki H,Quan C, Taniguchi M.
  • Journal Title: Int. Immunol. Volume: in press
  • Peer Reviewed
• [Presentation] A validation of the requirement for Vα14 NKT cells for tumor rejection using newly generated Traj18-deficient mice with undisturbed T cell receptor repertoire. (2015)
  • Author(s): Dashtsoodol N, Shigeura T, Watanabe T, Harada M, Kojo S, Endo T, Ohara O, Koseki H, Taniguchi M.
  • Organizer: CD1-MR1 2015
  • Place of Presentation: Mantra Lorne, Victoria, Australia
  • Year and Date: 2015-11-15
  • Int'l Joint Research
• [Presentation] Characterization of the cell with Th1-type NKT cell potential in the DN1 thymic fraction. (2013)
  • Author(s): Dashtsoodol N, Harada M, Endo TA, Ren Y, Seino K, Ohara O, Carey J, Germany-Partarrieu M, Taniguchi M.
  • Organizer: 7th INTERNATIONAL SYMPOSIUM ON CD1 AND NKT CELLS
  • Place of Presentation: Tours, France
• [Presentation] Transcription factor c-Maf is indispensable for the development of Interleukin-17 producing RORγt-positive invariant NKT cells. (2013)
  • Author(s): Dashtsoodol N, Ren Y, Harada M, Ishige A, Aihara M, Shigeura T, Ozawa R, Yamanaka H, Seino K, Taniguchi M.
  • Organizer: 7th INTERNATIONAL SYMPOSIUM ON CD1 AND NKT CELLS
  • Place of Presentation: Tours, France
• [Remarks] 統合生命医科学研究センター 免疫制御戦略研究グループ 研究紹介
  • URL: http://www.riken.jp/research/labs/ims/immune_reg/
• [Remarks] 統合生命医科学研究センター免疫制御戦略研究グループ 研究紹介
  • URL: http://www.riken.jp/research/labs/ims/immune_reg/